Antiplatelet pharmacology

• Components of the hemostatic system


  • Endothelium
  • Damaged endothelial
  • Vasospasm of vessels
  • Adhesion→ activation→ aggregation
  • Platelets
  • Coagulation system
  • Fibrinolytic system
• Thromboxane A2 (TXA2)


  • Synthesizes within platelets and released with platelet degranulation
  • Platelet aggregation
  • Vasoconstriction
  • Amplifies effect of thrombin
• Serotonin


  • Released from platelets
  • Platelet aggregation
  • Vasoconstriction
• Fibrinogen


  Ligand for the platelet glycoprotein 2b/3a receptor
• Aspirin


  • Irreversibly acetylates COX for the life of the platelet (~7 days)
  • COX catalyzes first step in production of prostaglandins
  • COX is responsible for formation of TXA2 and PGI2
  • Low dose→ selectivity for inhibiting TXA2
  • High dose→ does not increase antithrombotic efficacy
  • Increased inhibition of PGI2→ risk of bleeding increases
• Aspirin contraindications


  • Children or teens
  • Aspirin-exacerbated respiratory disease (AERD)
  • Samter's triad (asthma, rhinitis, nasal polyps)
• P2Y12 inhibitor uses


  • MI
  • Stroke
  • PAD
  • Chronic arterial occlusion
  • Percutaneous interventions
• Clopidogrel


  • Prodrug (CYP2C19)
  • Omeprazole may reduce effectiveness
  • Smoking increases effectiveness, CYP1A2
• Prasugrel contraindications


  • Active bleeding
  • History of stroke
• Dipyridamole


  • Weak platelet adhesion inhibitor
  • Inhibits uptake of adenosine
  • Inhibits formation of TXA2
  • Inhibits PDE3→ vasodilation
• Dipyridamole uses


  • Stroke prevention (with ASA)
  • Myocardial perfusion imaging with thallium
• Cilostazol ADRs


  • GI
  • Diarrhea
  • Headache
• GP 2b/3a inhibitors


  • Tirofiban
  • Eptifibatide
  • Block the final common pathway to platelet aggregation
  • Blocks GP 2b/3a receptor→ preventing fibrinogen binding→ inhibits platelet aggregation
  • Block platelet function regardless of what activated the platelet
• GP 2b/3a inhibitor monitoring parameters


  • HCT/HgB
  • Platelets
  • PT/aPTT
  • ACT
  • PCI
• GP 2b/3a inhibitor drug interactions


  • Other anti-platelets
  • Heparins
  • NSAIDs
  • Warfarin